ESTRO 36 Abstract Book

S993 ESTRO 36 _______________________________________________________________________________________________

Results These findings show that kinetics of DSBs significantly differ in hiPSCs, chondrocytes, and chondrocyte-like cells differentiated from hiPSCs. Nevertheless, the formation of DSBs in hiPSC-derived chondrocytes is similar to processes occurring in hiPSCs rather than in human articular chondrocytes. The hiPSCs and hiPSC-derived chondrocytes are very prone to DNA damage in comparison with fully mature chondrocytes. However, it is important to point out that hiPSC-derived chondrocytes possess more efficient DNA repair mechanisms resulting in the lower level of DSBs after 24h, in contrast to hiPSCs. Consequently, hiPSC-derived chondrocytes did not easily undergo apoptosis as hiPSCs. Nevertheless, the hiPSC- derived chondrocytes also reveal increased level of cells undergoing senescence. Conclusion The genetic integrity of pluripotent SCs and their derivatives is very relevant due to the unavoidable exposure of SCs to genotoxic and cytotoxic agents during diagnostic procedures, as well as during anti-cancer therapies. For that reason, further studies concerning the safety of stem and stem-derived cells treated with IR are EP-1809 Effect of thalidomide on radiation-induced urinary bladder dysfunction J. Kowaliuk 1 , E. Bozsaky 2 , S. Sarsarshahi 1 , P. Kuess 3 , W. Dörr 2 1 Medical University of Vienna, Department of Radiotherapy- ATRAB - Applied and Translational Radiobiology, Vienna, Austria 2 Medical University of Vienna, Department of Radiotherapy- ATRAB - Applied and Translational Radiobiology and Christian Doppler Laboratory for Medical Radiation Research for Radiation Oncology, Vienna, Austria 3 Medical University of Vienna, Department of Radiotherapy - Christian Doppler Laboratory for Medical Radiation Physics for Radiation Oncology, Vienna, Austria Purpose or Objective The urinary bladder represents an important organ at risk during of radiotherapy pelvic tumors. Exposure to significant radiation doses results in the impairment of the biological function, presenting as a decrease in bladder capacity. Patients suffer from dysuria, urgency, incontinence, and increased micturition frequency, including nocturia. The radiation response occurs in three distinct phases: a reversible, biphasic early response, a symptom-free latent phase and an irreversible late phase eventually resulting in fibrosis. Local inflammatory processes are significantly involved in the pathogenesis of radiation response, with a potentially central role of the transcription factor NF-κB. Therefore, thalidomide, a potent NF-κB inhibitor, is studied in a mouse model for its potential to prevent or alleviate bladder dysfunction. Material and Methods This preclinical study was performed in a well-established mouse model. Groups of female mice of the C3H/Neu strain were subjected to local single dose irradiation of the urinary bladder with graded doses in order to generate complete dose-effect curves. Bladder compliance was determined by transurethral cystotonometry - defining the bladder capacity at an intravesical pressure of 10 mm Hg - in 3-day intervals in the early response phase (day 0-30 p. irr) and subsequently at 4-week intervals until day 360. required. Funding: National Science Centre (2012/E/NZ3/01819) Greater Poland Cancer Centre (19/02/2016/PRB/WCO/010)

The “mouse toilet”, designed to record individual urinations of the mice for analyses of micturition frequency and volume per micturition, was used on a monthly basis. Thalidomide was applied intraperitoneally, at a daily dose of 100 mg/kg over various time intervals in early and latent phase. Results Preliminary results demonstrate that thalidomide clearly reduces radiation - induced functional urinary bladder changes. Daily administration from day 0 – day 15 or day 15 – day 30 significantly reduced the number of responding mice (response: >50 % reduction in bladder capacity). Furthermore, the maximum reduction in bladder capacity was less pronounced in thalidomide treated vs. only irradiated untreated mice. Conclusion The preliminary data indicate that thalidomide has a clear potential to alleviate radiation-induced urinary bladder function impairment in the early phase. This illustrated the crucial involvement of NF-κB in the pathogenesis of the early changes. This will further be confirmed in mechanistic, immunohistochemical investigations. The consequences of the early thalidomide treatment, as well as of administration in the latent phase, on late effects are subject to ongoing studies. Data will be presented. EP-1810 Both location and complexity of DNA damage contribute to radiation induced senescence J. Wang 1 1 Institute of Modern Physics- Chinese Academy of Sciences, Biophysics, Lanzhou, China Purpose or Objective Cellular senescence was involved in aging by irreversible loss of proliferative potential. It causes inhibition of cell growth and reduction of cellular function. However, the molecular bases of the DNA damage and their contribution to cellular senescence are not completely clear. The purpose of this study is to investigate the significant role of persistent DNA damage response (DDR) in cellular senescence induced by different kinds of ionizing radiation. Material and Methods By measuring senescence associated-β-galactosidase, cell proliferation, activity of Ki67, the number of XRCC1 foci and 53BP1 foci, we identified that heavy ions (including carbon ions, iron ions) and X-rays irradiation could induce senescence in human uveal melanoma 92–1 cells. Results We found that heavy ions were more effective at inducing senescence than X-rays. It was observed that with the repairing of DNA damage, the percentage of 53BP1 foci co- localized with telomeres continually increased and reached to 30% for X-rays at the 5th day after irradiation while the percentage of 53BP1 foci co-localized with telomeres remained steadily around 15% for carbon ions irradiation, implying that the persistent DNA damage induced by X-rays was preferentially associated with telomeric DNA and the telomere-favored persistent DNA damage mainly contributed to cellular senescence induced by X-rays. For heavy ions, less efficient repair of DNA damage was observed and most of the irreparable damage was the complex of single strand breaks and double strand breaks, suggesting that DNA damage induced by heavy ion was often complex and difficult to repair, thus presented as persistent DNA damage and pushed the cells into senescence. In contrast, DNA damage induced by X-rays was mostly repaired in 24 hours. Electronic Poster: Radiobiology track: Radiobiology of cancer (others)